This invention relates generally to the detection of radiation and more particularly to signal discrimination used with probes for the detecting of radiation in the cells of biological systems.
In the detection and/or treatment of certain diseases, e.g., cancer, radiopharmaceuticals such as monoclonal antibodies tagged with radioaotive isotopes (e.g., Iodine 125, Indium 111, Technetium 99m, etc.) are frequently injected into the body of the patient. These isotope-tagged antibodies tend to seek out particular tissues, e.g., the cancerous tissue. Gamma-ray detectors are then employed to detect the gamma-ray radiation emitted by the tagged antibodies to localize and/or provide an image of the radiation emitting tissue(s).
In order to expedite the localization of the tagged tissue, surgeons are increasingly turning to the use of hand-held radiation detecting probes. One such probe is commercially available from Care Wise Medical Products, Inc. of Morgan Hill, Calif. 95037, the assignee of this application, under the trademark ONCOPROBE. That probe is electrically connected to an analyzer/monitor.
The output of the ONCOPROBE device probe is a series of electrical pulses having a count or repetition rate, which is related to the counts per seconds of gamma-ray radiation received by it. The higher the electrical pulse rate, the greater the counts per seconds of received radiation. The electrical pulses are used by the analyzer to provide an audible output signal representative of the counts.
In U.S. Pat. No. 4,959,547, also assigned to the same assignee as this invention, there is disclosed a probe with an adjustment mechanism (i.e., collimator) for adjusting the solid angle through which the radiation may pass to the radiation detector, e.g., a crystal, within the probe's body. The collimating probe assists the surgeon by enabling him or her to reduce the angle through which radiation reaches the detector to localize smaller radiation sources or "hot spots" in a noise background.
A problem with the use of monoclonal antibodies tagged with radioactive isotopes to detect cancerous tumors is that the radioactivity tends to diffuse throughout the body and also concentrate particularly around certain organs and other parts of the body. Thus, approximately 35% of the injected radioactive isotope is absorbed in the liver, 20% is absorbed in the blood pool, and most of the remainder is diffused generally throughout the body. Only about 0.5% of the total available radiation is absorbed by, and is concentrated in, cancerous tumors. This results in a extremely high background level of radiation as compared to the available target signal. This is particularly true near the liver and other organs which have high concentrations of radiation, which makes the detection of cancer cells difficult.
The situation is further exacerbated by the fact that the background radiation is variable and uneven ("lumpy"), and can change rapidly as the probe is moved about by the surgeon.
During the localization procedure, the surgeon is guided by the sound produced by the analyzer connected to the probe. In this regard, pulses from the gamma-ray detector in the probe provide signals to the analyzer to modulate an audio tone so that the surgeon hears an audible signal whose repetition rate is proportional to the counts per second of radiation detected by the probe. The higher the audible repetition rate, the greater the counts per second of radiation detected.
At present, the problem of high background radiation is attempted to be neutralized or obviated by operator control, i.e., the instrument's operator sets the count threshold levels to remove or "null out" counts representative of background radiation, so that the remaining detected radiation represents the hot spots which the surgeon seeks ( i.e., the tagged tissue).
This method, while a step in the right direction, nevertheless leaves much to be desired. In this connection, with certain types of isotopes in common use, such as Iodine 125, which emits a 35 Ke V gamma in only 7% of its disintegrations resulting in low counts per second, a strong signal is about 20 counts per second, whereas the background radiation may be as high as 10 counts per second. Thus, when the background level, which is extremely variable, drops, radiation from hot spots is often not detected. Also, the setting of the threshold level is arbitrary and subject to error by the operator.
For systems which use Indium 111 and Technetium 99m, much higher radiation counts per second are available. Here, the gamma-ray detectors can produce repetition rates from 1 to 2 Hz up to 10,000 Hz. However, a problem with higher counts per second radiation levels is the sound discrimination ability of the human ear and brain. In this regard, human beings are able to discriminate between differences in repeating sounds very efficiently at low repetition rates, e.g., up to approximately 20 to 25 counts per second. However, humans are much less efficient at discriminating sounds at the higher repetition rates. Thus, the difference between a repetition rate of 5 versus 10 per second is easily discernable while the difference between a repetition rate of 120 to 150 is difficult for a human being to discern. Therefore, in addition to problems with strong and variable background radiation, even with target signals which are quite large, the ability of human beings to discriminate is poor at higher count rates.
An attempt to overcome this inherent limitation of humans by use of specialized techniques is disclosed in a report by Borgstrom et al. of the Division of Nuclear Medicine, Department of Radiology, University of Arizona entitled Detection of Small Radiation Sources: The Effect of Mode of Count-Rate Presentation (1989). That report was based on a study performed under a grant awarded by the National Cancer Institute, USPHS Grant No. C.A. 2347. Four methods were studied for the detection of small radiation sources. One method entailed the use of a rate meter to visually display the detected radiation rate. The second method entailed producing an audio signal (i.e., a "beep") at the detected repetition rate. The third method displayed the rate data on a cathode ray tube. The fourth method entailed use of a micro-processor to count and store the background radiation and to compare it to the incoming count rate. In accordance with that last method, the operator selected a threshold which is the background count plus an additional count set by the operator (a "delta"). If during the counting interval of 1/3 second duration taken at a suspected source site the count exceeds the background plus delta, a beeper is sounded until the end of the interval. As the count rate is increased, beeps become more frequent and have a longer duration.
It was found in the Borgstrom et al. study, that the fourth method, i.e., the method of utilizing the stored background count with the delta, was more efficient in detecting small radiation sources in the background than the other three modes of count-rate presentation. However, the fourth method of Borgstrom et al. still suffers from the fact that in practice, the radiation background levels encountered tend to be highly variable. Thus, if the background decreases in value, small radiation sources may be lost because the decreased value of the background plus the radiation source contribution are below the threshold setting plus the delta. Also the choice of the delta value is arbitrary and may not relate to a meaningful statistical variation in radiation.
Harris et al., in an article entitled A Csl (TI)-Crystal Surgical Scintillation Probe, Nucleonics, November, 1956, disclose an operative probe with a sound system from a multi-vibrator with a range of 12 CPS to 1300 CPS. An eight position selection switch provides a variation in sensitivity in steps of about a factor of three. However, the system described in this article sets a threshold level for discrimination against background radiation.
Harvey and Lancaster, in a paper entitled Technical and Clinical Characteristics of a Surgical Biopsy Probe, The Journal of Nuclear Medicine, 22:184-186 (1981), disclose an audible count rate indicator that produces a signal proportional to a difference in counting rates. In this case the probe is first placed over representative normal tissue to set background level and a threshold is set, so that all subsequent audible rate beeps are an indication of count rates in excess of the background value.
The efficiency and effectiveness of hand-held radiation probes by surgeons in locating cancerous tumors have been progressively improved since their initial use. Initially, Iodine isotopes with low radiation counts per second and low frequencies were used. Then higher radiation energy and higher counts per second isotopes, such as Indium 111 and Technetium 99m, were introduced. The shielding of probes has been improved and collimating probes have been introduced to better discriminate and obtain the radiation from the target cells. Also, energy discrimination techniques are used to eliminate stray radiation. These improvements have resulted in increasing the probability of finding very small tumors, in the range of 8 mm-10 mm in diameter, to 90% or better. However, as discussed above, by setting arbitrary thresholds which eliminate background noise, or by automatically setting thresholds with arbitrary deltas, additional valuable data and information, which could further improve the chances of finding very small tumors in high background radiation, is lost.
Furthermore, with isotopes emitting higher counts per second, the count ranges of the detected radiation become higher and human beings are not able to properly discriminate statistical differences in count rates.